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      Infection of dogs by Leishmania infantum elicits a general response of IgG subclasses

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          Abstract

          Leishmania infantum is the etiological agent of zoonotic visceral leishmaniasis. In endemic areas, canine infections are considered the main source of infection for human populations. Therefore, any control of human leishmaniasis must include the control of canine infections. Chemotherapy of leishmaniasis is inadequate and canine immunoprophylaxis has important limitations. Reports on the response of infected dogs are abundant but no clear picture of immune events has emerged. To shed some light on these shortcomings the specific IgG subclass response was followed in 20 Beagle dogs experimentally infected with L. infantum using monoclonal antibodies (MAb) specific for canine IgG 1, IgG 2, IgG 3 and IgG 4, along with ELISA and flow cytometry. Results showed that parasitic infection elicits a general response of all IgG subclasses, with a predominant IgG 1 response and without any evidence of IgG 1/IgG 2 dichotomy. These findings suggest that the inconsistent results reported previously could be related to the lack of specific reagents and not to the actual differences in the immune response of infected animals. Differential IgG subclass reactivity in ELISA and cytometry and the analysis of the reacting antigens could facilitate the diagnosis and prognosis of the disease and provide a useful tool for adequate therapeutics and vaccine development against leishmaniasis.

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          Most cited references58

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          Leishmaniasis Worldwide and Global Estimates of Its Incidence

          As part of a World Health Organization-led effort to update the empirical evidence base for the leishmaniases, national experts provided leishmaniasis case data for the last 5 years and information regarding treatment and control in their respective countries and a comprehensive literature review was conducted covering publications on leishmaniasis in 98 countries and three territories (see ‘Leishmaniasis Country Profiles Text S1, S2, S3, S4, S5, S6, S7, S8, S9, S10, S11, S12, S13, S14, S15, S16, S17, S18, S19, S20, S21, S22, S23, S24, S25, S26, S27, S28, S29, S30, S31, S32, S33, S34, S35, S36, S37, S38, S39, S40, S41, S42, S43, S44, S45, S46, S47, S48, S49, S50, S51, S52, S53, S54, S55, S56, S57, S58, S59, S60, S61, S62, S63, S64, S65, S66, S67, S68, S69, S70, S71, S72, S73, S74, S75, S76, S77, S78, S79, S80, S81, S82, S83, S84, S85, S86, S87, S88, S89, S90, S91, S92, S93, S94, S95, S96, S97, S98, S99, S100, S101’). Additional information was collated during meetings conducted at WHO regional level between 2007 and 2011. Two questionnaires regarding epidemiology and drug access were completed by experts and national program managers. Visceral and cutaneous leishmaniasis incidence ranges were estimated by country and epidemiological region based on reported incidence, underreporting rates if available, and the judgment of national and international experts. Based on these estimates, approximately 0.2 to 0.4 cases and 0.7 to 1.2 million VL and CL cases, respectively, occur each year. More than 90% of global VL cases occur in six countries: India, Bangladesh, Sudan, South Sudan, Ethiopia and Brazil. Cutaneous leishmaniasis is more widely distributed, with about one-third of cases occurring in each of three epidemiological regions, the Americas, the Mediterranean basin, and western Asia from the Middle East to Central Asia. The ten countries with the highest estimated case counts, Afghanistan, Algeria, Colombia, Brazil, Iran, Syria, Ethiopia, North Sudan, Costa Rica and Peru, together account for 70 to 75% of global estimated CL incidence. Mortality data were extremely sparse and generally represent hospital-based deaths only. Using an overall case-fatality rate of 10%, we reach a tentative estimate of 20,000 to 40,000 leishmaniasis deaths per year. Although the information is very poor in a number of countries, this is the first in-depth exercise to better estimate the real impact of leishmaniasis. These data should help to define control strategies and reinforce leishmaniasis advocacy.
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            Leishmaniasis

            Leishmaniasis is a poverty-related disease with two main clinical forms: visceral leishmaniasis and cutaneous leishmaniasis. An estimated 0·7-1 million new cases of leishmaniasis per year are reported from nearly 100 endemic countries. The number of reported visceral leishmaniasis cases has decreased substantially in the past decade as a result of better access to diagnosis and treatment and more intense vector control within an elimination initiative in Asia, although natural cycles in transmission intensity might play a role. In east Africa however, the case numbers of this fatal disease continue to be sustained. Increased conflict in endemic areas of cutaneous leishmaniasis and forced displacement has resulted in a surge in these endemic areas as well as clinics across the world. WHO lists leishmaniasis as one of the neglected tropical diseases for which the development of new treatments is a priority. Major evidence gaps remain, and new tools are needed before leishmaniasis can be definitively controlled.
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              Advantages of real-time PCR assay for diagnosis and monitoring of canine leishmaniosis.

              The aim of the present study is to highlight the advantages of real-time quantitative PCR intended to aid in the diagnosis and monitoring of canine leishmaniosis. Diagnosis of canine leishmaniosis is extremely challenging, especially in endemic areas, due to the diverse and non-specific clinical manifestations, and due to the high seroprevalence rate in sub-clinical dogs. Veterinarian clinicians are usually confronted with cases that are compatible with the disease, and with several diagnostic tests, sometimes with contradictory results. We have developed a new TaqMan assay, targeting the kinetoplast, applied to 44 samples of bone marrow aspirate or peripheral blood. The dynamic range of detection of Leishmania DNA was established in 7 logs and the limit of detection is 0.001 parasites in the PCR reaction. At the time of diagnosis parasitemia ranges from less than 1 to 10(7)parasites/ml. The ability to quantify the parasite burden allowed: (i) to elucidate the status of positive dogs by conventional PCR, although larger studies are necessary to clarify the dividing line between infection and disease, (ii) to estimate the kinetics of the parasite load and the different response to the treatment in a follow-up and (iii) to validate blood as less invasive sample for qPCR. The continuous data provided by real-time qPCR could solve the dilemma for the clinician managing cases of canine leishmaniosis by differentiating between Leishmania-infected dogs or dogs with active disease of leishmaniosis.
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                Author and article information

                Contributors
                jmalunda@ucm.es
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                2 November 2020
                2 November 2020
                2020
                : 10
                : 18826
                Affiliations
                [1 ]GRID grid.4795.f, ISNI 0000 0001 2157 7667, Department of Animal Health, Faculty of Veterinary Medicine, , Universidad Complutense, ; Madrid, Spain
                [2 ]GRID grid.413448.e, ISNI 0000 0000 9314 1427, Unidad de Inmunología Microbiana, , Instituto de Salud Carlos III, ; Carretera de Majadahonda-Pozuelo, Km.2.2, Majadahonda, Madrid, Spain
                [3 ]GRID grid.1025.6, ISNI 0000 0004 0436 6763, School of Veterinary and Life Sciences, , Murdoch University, ; Murdoch, WA Australia
                Article
                75569
                10.1038/s41598-020-75569-6
                7606601
                33139752
                913ee53d-ed4a-4d40-9141-9a8215855cb2
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 24 May 2020
                : 14 October 2020
                Categories
                Article
                Custom metadata
                © The Author(s) 2020

                Uncategorized
                parasitic infection,parasite host response,applied immunology,infection
                Uncategorized
                parasitic infection, parasite host response, applied immunology, infection

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